Toll/Interleukin-1 Receptor Domain-Containing Adapter Protein (TIRAP) Human Recombinant Protein

The innate immune system recognizes microbial pathogens through Toll-like receptors (TLRs), which identify pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns and all TLRs have a Toll-interleukin 1 receptor (TIR) domain, which is responsible for signal transduction. The protein encoded by this gene is a TIR adaptor protein involved in the TLR4 signaling pathway of the immune system. It activates NF-kappa-B, MAPK1, MAPK3 and JNK, which then results in cytokine secretion and the inflammatory response. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

TIRAP: an adapter protein involved in the TLR4 signaling pathway in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, ERK1, ERK2 and JNK, resulting in cytokine secretion and the inflammatory response. Homodimerizes. Also forms heterodimers with MyD88. Binds to TLR4 and IRAK2 via their respective TIR domains. Binds to PKR and TBK1. Does not interact with IRAK1, nor TLR9. Genetic variations in TIRAP can influence susceptibility or resistance to infectious diseases, including invasive pneumococcal disease, malaria and tuberculosis. Three isoforms of the human protein are produced by alternative splicing.

Protein type: Adaptor/scaffold

Chromosomal Location of Human Ortholog: 11q24.2

Cellular Component: nucleoplasm; intercellular bridge; endocytic vesicle; cytoplasm; plasma membrane; cytosol

Molecular Function: protein binding, bridging; phosphatidylinositol-4,5-bisphosphate binding; protein binding; protein homodimerization activity; protein kinase C binding; protein heterodimerization activity

Biological Process: I-kappaB kinase/NF-kappaB cascade; positive regulation of toll-like receptor 3 signaling pathway; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of interleukin-12 production; positive regulation of interleukin-6 biosynthetic process; positive regulation of toll-like receptor 4 signaling pathway; positive regulation of JNK cascade; response to lipopolysaccharide; positive regulation of tumor necrosis factor production; positive regulation of toll-like receptor 2 signaling pathway; regulation of innate immune response; toll-like receptor 2 signaling pathway; activation of NF-kappaB transcription factor; positive regulation of interleukin-8 production; MyD88-dependent toll-like receptor signaling pathway; defense response to Gram-positive bacterium; cell surface receptor linked signal transduction; positive regulation of interleukin-15 production; toll-like receptor signaling pathway; positive regulation of B cell proliferation; innate immune response; myeloid cell differentiation; regulation of interferon-beta production; inflammatory response; toll-like receptor 4 signaling pathway

Disease: Invasive Pneumococcal Disease, Recurrent Isolated, 1; Bacteremia, Susceptibility To, 1; Mycobacterium Tuberculosis, Susceptibility To; Malaria, Susceptibility To